Funding
We are very grateful for the funding we have had from the Alzheimer's Research UK, Alzheimer's Society, BBSRC, Cunningham Trust, EPSRC, Kirby Laing Foundation, MRC, Russell Trust, RS Macdonald Charitable Trust, SHERT/MRS, SULSA and the Wellcome Trust

Research interests

As Molecular Neurobiologists my group are interested in uncovering how proteins work in living cells. We have worked on a number of proteins that are involved in the formation and development of the mammalian nervous system and how they are affected in diseases such as Alzheimer’s disease and Cancer. Our approach to understand these processes has been truly interdisciplinary as we publish in all science areas of Biology, Chemistry and Physics. For a lay summary then you can watch my inaugural lecture on: http://biology.st-andrews.ac.uk/newsItem.aspx?ni=2109

A) Biochemistry and Cellular Biology: The consequences of mitochondrial beta-amyloid in Alzheimer’s disease and the role of Willin/FRMD6 in the activation of the Hippo signalling pathway

Amyloid binding alcohol dehydrogenase (ABAD) and Cyclophilin D (CypD) are mitochondrial binding sites for the toxic peptide, beta-amyloid (Muirhead et al., 2010a, Borger et al., 2013). Alzheimer patients have increased expression levels of ABAD and CypD and their interaction with beta-amyloid results in neuronal cell death (Lustbader et al., 2004; Du et al., 2008). Intriguingly upon binding beta-amyloid, ABAD translocates from the endoplasmic reticulum to the inner face of the plasma membrane, but the significance of these phenomena is unknown. Information concerning the structure of ABAD will be of great significance. Drugs designed to prevent the interaction of the beta-amyloid peptide to ABAD and CypD could potentially prevent apoptosis of neurons. In collaboration, we have purified, crystallized and solved the three dimensional structure of this important protein (Powell et al., 2000; Lustbader et al., 2004). Also see BBC web site http://news.bbc.co.uk/1/hi/health/3628319.stm. We have developed cellular based assays to screen novel drugs which interfere with the beta-amyloid-ABAD interaction (Muirhead et al, 2010b) which are hoped to be developed for the treatment of Alzheimer's disease. We have also, using proteomics technology, identified novel proteins which become activated in Alzheimer's patients (Yao et al., 2007; Ren et al., 2008; Yao et al., 2011; Doherty et al., 2013) also see BBC web site http://news.bbc.co.uk/1/hi/scotland/edinburgh_and_east/6911831.stm). In a separate project in collaboration with the Universities of Edinburgh, Bristol and California, we have also discovered that pet cats also have molecular characteristics that are associated with Alzheimer's disease (Gunn-Moore et al., 2006; Gunn-Moore et al., 2010). Also see BBC website: http://news.bbc.co.uk/1/hi/scotland/6212080.stm.

In addition, as part of previous studies into the L1 family of cell adhesion molecules, we have identified novel proteins and new protein-protein interactions between cell adhesion molecules and cytoplasmic proteins (Davey et al., 2005; Gunn-Moore et al., 2006; Herron et al., 2009). This led us to discover a new member of the 4.1 superfamily of proteins. This protein Willin (also termed FRMD6) (Gunn-Moore et al., 2005) appears to be able to activate the Hippo signalling pathway, and has a potential role as acting as a novel tumour suppressor (Madan et al., 2006; Schlecht et al., 2012, Angus et al., 2012; see also http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-13808568). We have also shown that KIBRA, another upstream component of the Hippo pathway, activates this pathway via a new and novel mechanism (Moleirinho et al., 2013). More recently, Willin and KIBRA have both been linked to the pathogenesis of Alzheimer’s Disease.

B) Biophotonics: Photoporation and the manipulation of cells with light

It has been known for a long time that cells can respond to light, for example unicellular organisms are known that can move towards a light source (phototaxis) or the photoreceptor cell in the mammalian retina that detects light and produces a signalling cascade (phototransduction), giving vision. Recent studies, however, indicate that the response of whole cells to light is a much more widely distributed phenomenon than previously appreciated. It is now apparent that cells can be influenced by light in diverse ways, for example by influencing their growth or modifying their membrane structure allowing large molecules to cross cell membranes. Optical tweezer techniques can be used for cell manipulation and sorting. Furthermore, the optical scattering and absorption properties of cells can be used for detection purposes, either using plane waves, microcavity configurations, Bessel beams or Raman techniques. In a major collaboration between the Schools of Physics, Biology and Medicine, we are investigating how light can influence and manipulate both cellular and sub-cellular biological material (see University of St Andrews Biophotonics. In particular, we have developed a novel transfection technique that allows the selective introduction of genetic material into a variety of mammalian cells (e.g. see Paterson et al., 2005; Stevenson et al., 2006; Tsampoula et al., 2007; Cizmar et al., 2008; Torres et al., 2010; Mthunzi et al., 2010). We have also developed this technology for use with optic fibres (Tsampoula et al., 2008; Nan et al., 2010). In another example of truly interdisciplinary research we have developed an ability to manipulate positively the growth of neuronal growth cones by use of laser light (Stevenson et al., 2006; Carnegie et al., 2008; Carnegie et al., 2009). This work has now been strengthened by a SULSA funded Cell Technologist (see http://photon.st-andrews.ac.uk/sulsa/) who is developing many of these techniques for researchers outside of St Andrews (for example see: http://www.scotland.gov.uk/News/Releases/2012/06/scottish-californian-stem21062012).